mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Repurposed Drugs (TACTIC-R)
TACTIC-R
1 other identifier
interventional
1,167
1 country
1
Brief Summary
TACTIC-R is a randomised, parallel arm, open-label platform trial for investigating potential treatment for COVID-19 disease. While SARS-CoV infection evades detection by the immune system in the first 24 hours of infection, it ultimately produces a massive immune system response in the subgroup of people who develop severe complications. Most tissue damage following infection with COVID19 appears to be due to a later, exaggerated, host immune response. This leads to lung and sometimes multi-organ damage. Most people who develop these severe complications still have virus present in their respiratory tract at the time-point when the disease starts to evolve. Immune modulation in the presence of active infection has potential to cause more harm than benefit. Safety considerations when studying immune modulation strategies are paramount. Therefore, this study proposes to assess the efficacy of immunomodulatory agents that target dysregulated immune response that drive the severe lung, and other organ, damage. The medications investigated for efficacy in this trial are Baricitinib and Ravulizumab.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4 covid19
Started May 2020
Longer than P75 for phase_4 covid19
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 8, 2020
CompletedStudy Start
First participant enrolled
May 8, 2020
CompletedFirst Posted
Study publicly available on registry
May 15, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 7, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2022
CompletedMay 18, 2020
May 1, 2020
12 months
May 8, 2020
May 14, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Time to incidence of the composite endpoint of: Death, Mechanical ventilation, ECMO, Cardiovascular organ support, or Renal failure
Number of days taken for occurrence of one of the following events: 1. Death 2. Mechanical ventilation 3. Extracorporeal membrane oxygenation (ECMO) 4. Cardiovascular organ support (balloon pump or inotropes) 5. Renal failure (estimated creatinine clearance (by Cockcroft-Gault formula) \<15 ml /min/1.73m\^2), haemofiltration or dialysis
up to Day 14
Secondary Outcomes (8)
Change in clinical status as assessed on 7-point ordinal scale compared to baseline
14 days
Proportion of patients with adverse events of special interest in each treatment arm
14 days
Time to Sp02 >94% on room air
14 days
Time to first negative SARS-CoV2 PCR
14 days
Duration of oxygen therapy
14 days
- +3 more secondary outcomes
Study Arms (3)
Standard of care
ACTIVE COMPARATORStandard of care
Ravulizumab + Standard of care
EXPERIMENTALRavulizumab IV (adjusted to weight, Day 1 only)
Baricitinib + Standard of care
EXPERIMENTALBaricitinib PO OD (4mg, Days 1-14)
Interventions
Ravulizumab (Ultomiris, Alexion Pharmaceuticals) is a monoclonal antibody that binds to terminal complement protein C5 and prevents the complement-mediated destruction of cells. It is administered by intravenous infusion. Ravulizumab has a marketing authorisation in the UK for treating Paroxysmal Nocturnal Haemoglobinuria in adults.
Baricitinib is administered orally once daily. It is licensed for treatment of rheumatoid arthritis, it is a relatively fast acting disease modifying anti-rheumatic drug and has the potential to be scaled up for use for a pandemic.
Eligibility Criteria
You may qualify if:
- To be included in the trial the participant must:
- Be aged 18 and over
- Have clinical picture strongly suggestive of COVID-19-related (with/without positive COVID-19 test) AND
- Risk count (as defined below) \>3 OR
- ≥ 3 if risk count includes "Radiographic severity score \>3"
- Be considered an appropriate subject for intervention with immunomodulatory in the opinion of the supervising clinician
- Be able to be maintained on venous thromboembolism prophylaxis or current maintenance therapy during inpatient dosing period, according to local guidelines
You may not qualify if:
- Inability to supply direct informed consent or assent from Next of Kin or Independent Healthcare Provider on behalf of patient
- Mechanical ventilation at time of prior to dosing
- Contraindications to study drugs, including hypersensitivity to the active substances or any of the excipients
- Currently on any of the study investigational medicinal products
- Known unresolved Neisseria meningitidis infection
- Unwilling to be vaccinated against Neisseria meningitidis or receive prophylactic antibiotic cover until 2 weeks after vaccination
- Known active tuberculosis (no blood screening required)
- Known active Hepatitis B or C (no blood screening required); active varicella zoster
- Concurrent participation in any interventional clinical trial including COVID-19-related disease trials (observational studies allowed)
- Patient moribund at presentation or screening
- Pregnancy at screening (or unwillingness to adhere to pregnancy advice in protocol)
- Unwillingness to adhere to breastfeeding advice in protocol
- Either alanine transaminase or aspartate transaminase (ALT or AST) \> 5 times the upper limit of normal
- Stage 4 severe chronic kidney disease or requiring dialysis (i.e. Cockcroft Gault estimated creatinine clearance \< 30 ml /min/1.73 m\^2)
- Currently receiving probenecid or chronic IVIG treatment
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Cambridge University Hospitals NHS Foundation Trust
Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom
Related Publications (3)
Hall FC, Cheriyan J, Cope AP, Galloway J, Wilkinson I, Bond S, Norton S, Banham-Hall E, Bayes H, Kostapanos M, Nodale M, Petchey WG, Sheeran T, Underwood J, Jayne DR; TACTIC-R Investigators Group. Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial. Lancet Respir Med. 2023 Dec;11(12):1064-1074. doi: 10.1016/S2213-2600(23)00376-4. Epub 2023 Nov 14.
PMID: 37977159DERIVEDKreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
PMID: 34473343DERIVEDKulkarni S, Fisk M, Kostapanos M, Banham-Hall E, Bond S, Hernan-Sancho E, Norton S, Cheriyan J, Cope A, Galloway J, Hall F, Jayne D, Wilkinson IB. Repurposed immunomodulatory drugs for Covid-19 in pre-ICu patients - mulTi-Arm Therapeutic study in pre-ICu patients admitted with Covid-19 - Repurposed Drugs (TACTIC-R): A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jul 8;21(1):626. doi: 10.1186/s13063-020-04535-4.
PMID: 32641154DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Frances Hall Hall, FRCP (UK), D.Phil
Cambridge University Hospitals NHS Foundation Trust
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Consultant Rheumatologist
Study Record Dates
First Submitted
May 8, 2020
First Posted
May 15, 2020
Study Start
May 8, 2020
Primary Completion
May 7, 2021
Study Completion
May 1, 2022
Last Updated
May 18, 2020
Record last verified: 2020-05